Most AD mouse models overexpress a mutated form of the human APP gene, a combination of mutated APP and PS1, or a combination of APP, PS1 and P301L (a tau mutation causing frontotemporal dementia) (reviewed in [ 101, 102]).
In humans, the presence of the P301S mutation in the Tau gene leads to a progressive tauopathy causing frontotemporal dementia (Bugiani et al., 1999).
GRN gene mutations were found to cause frontotemporal dementia (Baker et al., 2006; Cruts et al., 2006) and have been associated with other neurodegenerative diseases, such as Parkinson's disease, Creutzfeldt-Jakob disease, motor neuron disease, and Alzheimer's disease (Baker and Manuelidis, 2003; Lopez de Munain et al., 2008; Malaspina et al., 2001; Vercellino et al., 2011).
Progranulin (GRN) mutations causing haploinsufficiency are a major cause of frontotemporal lobar degeneration (FTLD-TDP).
The link between tau and neurodegeneration was confirmed with the discovery of mutations in the tau gene, MAPT, that cause frontotemporal dementia (FTD) with tau pathology (2, 3).
Interestingly, mutations in Grn have recently been discovered to cause frontotemporal dementia linked to chromosome 17 (FTD-17) (Baker et al 2006; Cruts et al 2006; Mukherjee et al 2006).
Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T).
More than 40 mutations in the MAPT gene have been also found to cause frontotemporal dementia with parkinsonism-17 (FTDP-17) [ 41].
Besides, mutation at the gene of GEP affects neuron survival and causes frontotemporal dementia (10, 11).
Individuals with these mutations exhibit tau-negative, but ubiquitin-positive, inclusions in their brain that eventually cause frontotemporal dementia.
